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Title: Tetratricopeptide repeat domain 9A modulates anxiety-like behavior in female mice
Authors: Lim, Lee Wei
Shrestha, Smeeta
Or, Yu Zuan
Tan, Shawn Zheng Kai
Chung, Hwa Hwa
Sun, Yang
Lim, Chew Leng
Khairuddin, Sharafuddin
Lufkin, Thomas
Lin, Valerie Chun Ling
Keywords: DRNTU::Science::Biological sciences
Tetratricopeptide Repeat Protein 9A
Anxiety Disorders
Issue Date: 2016
Source: Lim, L. W., Shrestha, S., Or, Y. Z., Tan, S. Z. K., Chung, H. H., Sun, Y., . . . Lin, V. C. L. (2016). Tetratricopeptide repeat domain 9A modulates anxiety-like behavior in female mice. Scientific Reports, 6,37568-. doi:10.1038/srep37568
Series/Report no.: Scientific Reports
Abstract: Tetratricopeptide repeat domain 9A (TTC9A) expression is abundantly expressed in the brain. Previous studies in TTC9A knockout (TTC9A−/−) mice have indicated that TTC9A negatively regulates the action of estrogen. In this study we investigated the role of TTC9A on anxiety-like behavior through its functional interaction with estrogen using the TTC9A−/− mice model. A battery of tests on anxiety-related behaviors was conducted. Our results demonstrated that TTC9A−/− mice exhibited an increase in anxiety-like behaviors compared to the wild type TTC9A+/+ mice. This difference was abolished after ovariectomy, and administration of 17-β-estradiol benzoate (EB) restored this escalated anxiety-like behavior in TTC9A−/− mice. Since serotonin is well-known to be the key neuromodulator involved in anxiety behaviors, the mRNA levels of tryptophan hydroxylase (TPH) 1, TPH2 (both are involved in serotonin synthesis), and serotonin transporter (5-HTT) were measured in the ventromedial prefrontal cortex (vmPFC) and dorsal raphe nucleus (DRN). Interestingly, the heightened anxiety in TTC9A−/− mice under EB influence is consistent with a greater induction of TPH 2, and 5-HTT by EB in DRN that play key roles in emotion regulation. In conclusion, our data indicate that TTC9A modulates the anxiety-related behaviors through modulation of estrogen action on the serotonergic system in the DRN.
DOI: 10.1038/srep37568
Rights: © 2016 The Authors (Nature Publishing Group). This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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